1. Soluble Siglec-5 associates to PSGL-1 and displays anti-inflammatory activity
- Author
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Pepin, Marion, Mezouar, Soraya, Pegon, Julie, Muczynski, Vincent, Adam, Frédéric, Bianchini, Elsa P, Bazaa, Amine, Proulle, Valerie, Rupin, Alain, Paysant, Jerome, Panicot-Dubois, Laurence, Christophe, Olivier D., Dubois, Christophe, Lenting, Peter J, Denis, Cécile V, Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Université Paris-Sud - Paris 11 (UP11)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut de Recherches Internationales Servier [Suresnes] (IRIS), The study was financially supported by a PhD-research grant from Institut Servier & Association Nationale de la Recherche Technique (Contrat CIFRE) to JPe, and an Inserm-Poste d’Accueil-grant (# ASC13101LSA) to MP., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
MESH: Anti-Inflammatory Agents/pharmacology ,E-SELECTIN LIGAND-1 ,[SDV]Life Sciences [q-bio] ,Anti-Inflammatory Agents ,MESH: Membrane Glycoproteins/genetics ,MESH: Antigens, Differentiation, Myelomonocytic/metabolism ,MESH: Lectins/metabolism ,MESH: Antigens, CD/pharmacology ,MESH: Leukocytes, Mononuclear/drug effects ,Lectins ,MESH: Animals ,MYELOID CELLS ,MESH: E-Selectin/metabolism ,NEUTROPHILS ,IN-VIVO ,MESH: Inflammation/drug therapy ,Membrane Glycoproteins ,MESH: Inflammation/chemically induced ,MESH: Inflammation/pathology ,MESH: Membrane Glycoproteins/metabolism ,MESH: Leukocyte Rolling/physiology ,P-Selectin ,Female ,E-Selectin ,MESH: Leukocytes, Mononuclear/metabolism ,CD33-RELATED SIGLECS ,VON-WILLEBRAND-FACTOR ,MESH: Lectins/pharmacology ,Antigens, Differentiation, Myelomonocytic ,MESH: Antigens, Differentiation, Myelomonocytic/pharmacology ,MESH: Tumor Necrosis Factor-alpha/toxicity ,GLYCOPROTEIN LIGAND ,MESH: Antigens, CD/metabolism ,Article ,MESH: Mice, Inbred C57BL ,Antigens, CD ,Animals ,Humans ,Leukocyte Rolling ,Protein Interaction Domains and Motifs ,MESH: Antigens, Differentiation, Myelomonocytic/genetics ,SIALIC-ACID ,Inflammation ,MESH: Protein Interaction Domains and Motifs ,MESH: Humans ,Tumor Necrosis Factor-alpha ,MESH: Lectins/genetics ,MESH: Solubility ,Mice, Inbred C57BL ,Disease Models, Animal ,Solubility ,Leukocytes, Mononuclear ,MESH: Antigens, CD/genetics ,IMMUNE-SYSTEM ,MESH: Disease Models, Animal ,MESH: Female ,MESH: P-Selectin/metabolism - Abstract
International audience; Interactions between endothelial selectins and the leukocyte counter-receptor PSGL1 mediates leukocyte recruitment to inflammation sites. PSGL1 is highly sialylated, making it a potential ligand for Siglec-5, a leukocyte-receptor that recognizes sialic acid structures. Binding assays using soluble Siglec-5 variants (sSiglec-5/C4BP and sSiglec-5/Fc) revealed a dose- and calcium-dependent binding to PSGL1. Pre-treatment of PSGL1 with sialidase reduced Siglec-5 binding by 79 ± 4%. In confocal immune-fluorescence assays, we observed that 50% of Peripheral Blood Mononuclear Cells (PBMCs) simultaneously express PSGL1 and Siglec-5. Duolink-proximity ligation analysis demonstrated that PSGL1 and Siglec-5 are in close proximity (
- Published
- 2016
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